Overall Abstract The Phase I COBRE at Mississippi State University (MSU) has catalyzed a transformation in the biomedical research enterprise, particularly in the research focus area of the COBRE, pathogen-host interactions. In the CVM Basic Sciences Department, where most COBRE investigators worked, the research culture has changed; 19 of 20 faculty members now have competitive extramural funding. Furthermore, the total NIH funding amount at Mississippi State University has increased from about $1.4 million in 2012 (just before the Phase I COBRE began) to about $5.4 million in 2016 (year 4 of the Phase I COBRE). Two of our Phase I investigators have graduated to independent status, and all have obtained significant levels of competitive extramural funding. In fact, these two independent Phase I investigators will serve on the Leadership Team in Phase II, which will continue relationships between Phase I and Phase II investigators to build functional teams that will be competitive for collaborative funding efforts. Continuing the transformation of biomedical research at MSU to yield a self-sustaining high level research enterprise is the goal of the Phase II COBRE described in this application. We have identified 5 excellent investigators (two of whom were hired during Phase I) to lead research projects in the Phase II COBRE. The projects include sufficient commonality to allow synergy, and all are novel and have the potential to open new avenues of investigation. For example, two projects focus on vector borne diseases, three projects investigate the role of microbial metabolic adaptations in virulence, and two projects involve Staphylococcus aureus. One of the most positive characteristics of our investigators is the spontaneous development of collaborations between Phase I and Phase II investigators, which has occurred even before the beginning of Phase II. Plans for Phase II take advantage of this by deliberately encouraging continued interactions between Phase I and Phase II investigators both in mentoring and in research collaboration. Each investigator in Phase II has identified a distinguished scientist who is a leader in his/her field of study to serve as an external mentor. Internal mentors (from MSU) will serve as advisors in both scientific areas and in grant writing. All members of the distinguished External Advisory Committee from Phase I have agreed to serve in the same role in Phase II. With funds from Phase I, physical facilities and research infrastructure have been substantially improved by purchase of major equipment, renovation of the HVAC system of 4 labs, and addition of 6 Biological Safety Cabinets. The support of MSU for research in pathogen-host interactions is also illustrated by the university?s substantial investment to acquire a BSL-3 modular lab (1200 square feet with 3 separate labs), which has been commissioned and should be operational by the summer of 2018. A major user will be one of our COBRE Phase I investigators. The proposed Phase II COBRE will allow initiatives begun in Phase I to continue and establish a critical mass of well-funded investigators who can conduct high impact research.